Ongoing studies to determine if the repeated intravenous infusions of cocaine affect the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in rats were completed. We found that the ability of the HPA axis to mount a normal response to the repeated administrations of the drug was intact. Thus, ACTH and corticosterone both increase initially after the first injection of cocaine. Corticosterone, with a longer half-life in plasma, then prevents the further CRH-mediated release of ACTH. In addition, the corticotrope responds normally to the release of arginine vasopressin from the posterior pituitary that is induced by blood volume depletion; and the corticosterone response occurred only in rats in which the anterior pituitary gland was present. Because repeated stimulation of the HPA axis by cocaine does not impair its response to the repeated stress that can be induced by the drug, it is likely that the immunosuppressive actions of cocaine are not mediated by the HPA system. Studies of the long-term endocrine effects of the prenatal administration of cocaine were also continued. Prolactin is a hormone normally inhibited by hypothalamic dopamine. The basal prolactin levels in males from mothers treated with cocaine throughout pregnancy, were 60% higher than in controls. Growth hormone, which is regulated primarily by peptidergic factors, was unaffected. Decreasing the dose of cocaine or limiting its administration to gestational days 8-22 resulted in normal basal levels of prolactin in the adult rats. These results suggest that prenatal exposure to a high dose of cocaine early in pregnancy can significantly affect the regulation of prolactin in adult rats and that there may be a critical period in early gestation in which cocaine can influence the development of at least one dopaminergic system such that changes in the regulation of prolactin persist into adulthood. We are currently using autoradiographic methods to determine if the prenatal treatments affected the binding of the dopamine transporter in the forebrain of these rats.